Risk of not receiving 2nd line therapy is high in EGFR mt+ patients: Real world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients

Introduction Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKIʼs Erlotinib/Gefitinib. The number of patients switching from 1st gen. to 3rd gen. TKI (30%) appeared to be low and it is questionable whether these data represent real world sequencing treatment patterns. Therefore, we investigated the sequence pattern, i.e. the percentage of 2nd line therapy in EGFR mt+ pts in 3 certified lung cancer centers in Germany.

Methods Data of 912 of 1477 pts tested for EGFR mutations (treated in Oldenburg, Bremen and Hamburg) were analyzed between 2009 – 2017. 140/144 pts with an activating EGFR mutation (16%) and treated with systemic therapy (4 pts received no therapy) were identified and their treatments were captured as well as their outcome. 36 pts were treated before accessibility to 3rd generation TKI and 104 pts after accessibility to 3rd generation TKI.

Results 130/140 pts were treated with 1st line TKI and 10 received 1st line chemotherapy. 17 pts are still on 1st line TKI, 8 pts were lost to follow-up, 3 pts died while on 1st line TKI. 112 pts were candidates for 2nd line therapy. 34/112 (30%) of these pts did not receive 2nd line therapy. Causes for not receiving 2nd line therapy were pts refusal (n = 2), bad PS (n = 26) frequently due to CNS metastases, fast progression and death (n = 6). After accessibility of 3rd generation TKI, 20 of 66 (30%) pts did not receive 2nd line therapy. Median OS of the overall cohort was 27 months (n = 140), median OS of pts receiving 2nd line (n = 78) vs. no 2nd line (n = 62) was 36 vs. 14 months (p < 0.0001). After accessibility of 3rd generation TKI 30/104 pts (29%) receive a 3rd generation TKI after 1st line or 2nd line therapy. Median OS of pts receiving (n = 30) and not receiving 3rd gen. TKI (n = 110) was 55 months vs. 22 months (p < 0.0001).

Conclusion In real world, a significant number of pts treated with 1st or 2nd generation TKI do not reach 2nd line therapy even when 3rd generation TKI were accessible. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS and lack of possibility to test for T790M in the minority of cases (n = 28/66, 42% were not tested). These data, although favorable for the small and very selected cohort of pts treated with Osimertinib, might argue for the most effective therapy in 1st line for pts with EGFR mt+ tumors.